Daily Respiratory Research Analysis
Three high-impact studies in respiratory medicine span interventional cardiopulmonary care, infectious disease prevention, and antimicrobial stewardship. A nationwide Japanese registry shows balloon pulmonary angioplasty (BPA) delivers robust hemodynamic benefits with low periprocedural mortality across hospital volumes, though severe complications are fewer in high-volume centers. Modeling from Latin America and the Caribbean optimizes timing of RSV passive immunization, while a multicenter ana
Summary
Three high-impact studies in respiratory medicine span interventional cardiopulmonary care, infectious disease prevention, and antimicrobial stewardship. A nationwide Japanese registry shows balloon pulmonary angioplasty (BPA) delivers robust hemodynamic benefits with low periprocedural mortality across hospital volumes, though severe complications are fewer in high-volume centers. Modeling from Latin America and the Caribbean optimizes timing of RSV passive immunization, while a multicenter analysis links higher cumulative corticosteroid dosing in non-HIV Pneumocystis pneumonia to increased mortality without respiratory benefit.
Research Themes
- Pulmonary vascular interventions and health system volume–outcome relationships
- Seasonality-informed prevention strategies for pediatric RSV
- Risk–benefit reassessment of adjunctive corticosteroids in opportunistic pneumonia
Selected Articles
1. Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: A Nationwide Prospective Multicenter Registry in Japan (J-BPA).
In this nationwide, prospective registry of 1202 CTEPH patients undergoing 5207 BPA procedures across 44 hospitals, BPA substantially improved hemodynamics (55.6% PVR reduction) with 0.2% periprocedural mortality. Efficacy and mortality were comparable between low- and high-volume centers, but severe complications were significantly less frequent in high-volume hospitals.
Impact: This is the largest prospective assessment of contemporary BPA across a national health system, demonstrating broad reproducibility with strong safety signals that are volume-dependent for severe complications.
Clinical Implications: BPA can be safely expanded beyond expert centers with comparable efficacy and very low periprocedural mortality; however, complex cases and training should be concentrated in high-volume centers to minimize severe complications.
Key Findings
- Among 1202 patients (44 hospitals), BPA reduced pulmonary vascular resistance by 55.6% with 0.2% periprocedural mortality.
- Low-volume hospitals conducted 40.8% of procedures; efficacy and periprocedural mortality did not differ by volume.
- Severe complications were significantly less frequent in high-volume hospitals (severe lung injury 0.3% vs 1.3%; balloon overdilatation 0.67% vs 1.7%; ventilation 0.3% vs 1.5%).
Methodological Strengths
- Prospective nationwide multicenter registry with large sample size (n=1202) and 5207 procedures
- Predefined volume categories aligned with international consensus (WSPH) enabling meaningful comparisons
Limitations
- Non-randomized observational design with potential residual confounding and case-mix differences
- Generalizability outside Japan and long-term outcomes beyond registry follow-up are not fully defined
Future Directions: Develop standardized training and referral networks to reduce severe complications in low-volume centers; conduct long-term outcome studies and cost-effectiveness analyses of BPA expansion.
BACKGROUND: Over the past decade, balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension has shown improved outcomes with procedural refinement in expert hospitals with high procedural volume. Whether the outcomes of BPA are reproducible in hospitals with limited procedural volumes remains unknown. The Japan BPA registry was designed to assess the outcomes of contemporary BPA from a nationwide perspective, including hospitals with low treatment volume. METHODS: This prospective multicenter registry enrolled 1202 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent BPA at 44 hospitals between April 2018 and March 2023. We assessed the efficacy and safety of BPA and survival rates, comparing high- and low-volume hospitals based on the BPA center definition (≥50 procedures per year) from the seventh World Symposium on Pulmonary Hypertension. RESULTS: A total of 5207 procedures were performed. Thirty-five low-volume hospitals (79.5%) performed 40.8% of all BPA procedures. BPA significantly improved symptoms, clinical parameters, and hemodynamics (55.6% reduction in pulmonary vascular resistance), with 0.2% periprocedural BPA-related mortality. Severe lung injury (0.3%), balloon overdilatation (0.67%), and mechanical ventilation (0.3%) were less common in high-volume hospitals than in low-volume hospitals (1.3%, 1.7%, and 1.5%, respectively; CONCLUSIONS: This nationwide registry demonstrated the outcomes of contemporary BPA in patients with chronic thromboembolic pulmonary hypertension. No significant differences were observed in efficacy and periprocedural mortality between low- and high-volume hospitals. However, the significantly lower rate of severe complications in high-volume hospitals indicates that BPA may be safer in high-volume hospitals.
2. Implications of respiratory syncytial virus seasonality for the timing of passive immunisation scenarios in Latin America and the caribbean - a cross-sectional modelling study.
Using 2010–2019 surveillance from 28 countries, RSV epidemics showed south-to-north progression and year-round circulation in the tropics. Seasonally timed or year-round passive immunization strategies avert 55–61% of RSV-ALRI in infants at 80% coverage, with combined maternal vaccine plus long-acting monoclonal antibody performing well in subtropical settings.
Impact: This study translates regional seasonality into actionable immunization windows, quantifying the preventable burden and informing policy on deploying maternal vaccination and long-acting antibodies.
Clinical Implications: Optimize timing of maternal RSV vaccines and long-acting monoclonal antibodies by climate zone: seasonal campaigns in temperate zones, year-round programs in tropics, and combined strategies in subtropics to maximize infant protection.
Key Findings
- 317,951 RSV-positive samples (12.6% positivity) were reported across 28 countries (2010–2019), with year-round epidemics in tropics and seasonal peaks progressing south-to-north.
- At 80% coverage, long-acting monoclonal antibodies could avert 61.3% (temperate exemplar) and 55% (tropical exemplar) of RSV-ALRI in infants <12 months.
- Combined maternal vaccination plus long-acting mAb in subtropical settings averted 57.3% of RSV-ALRI; year-round campaigns are preferred in the tropics.
Methodological Strengths
- Region-specific seasonality characterization using multi-country surveillance over a decade
- Scenario modeling that incorporates protection duration, uptake, and varied implementation windows
Limitations
- Model-based estimates depend on assumptions about efficacy, coverage, and duration, which may vary by setting
- Surveillance heterogeneity and under-ascertainment can affect seasonality and burden estimates
Future Directions: Prospective evaluation of real-world implementation timing, integration with maternal services, and head-to-head comparisons of seasonal versus year-round strategies across climate zones.
BACKGROUND: The variation in respiratory syncytial virus (RSV) seasonality presents challenges for the timing of RSV prophylaxis. Prevention policies must consider seasonal dynamics to protect infants from severe RSV infections. We evaluated the timing and impact of passive immunisation on birth cohorts in Latin America and the Caribbean, accounting for RSV seasonality, duration of protection and uptake. METHODS: We characterised the 2010-2019 RSV seasonality by climate region using a moving averages-based method and surveillance data and identified newborns eligible for passive RSV immunisation under varied assumptions of protection duration and strategies. Lastly, we explored different intervention time windows and estimated RSV-associated acute lower respiratory infections (ALRI) averted among newborns. FINDINGS: In 2010-2019, 28 countries reported 317,951 RSV-positive respiratory samples (12.6% RSV positivity). RSV epidemics followed a south-to-north progression, with onset ranging from March to November in subtropical climates, and year-round epidemics in the tropics. Seasonal immunisation benefited newborns born during January-September in temperate countries, while those born year-round in the tropics benefited from immunisation during at least one epidemic. Year-round vaccination covered newborns for at least one season; long-acting monoclonal antibodies (mAb) administered at five months to infants of immunised mothers extended protection through the remaining season. Year-round campaigns suited tropical climates. At 80% coverage, 61.3% (95% CI 60.7-67) and 55% (95% CI 55.0-56.0) RSV-ALRI cases among 0- < 12 months were averted through mAb in exemplar temperate and tropical countries, respectively. In subtropical countries, combined RSV maternal vaccination and long-acting mAb averted 57.3% (95%CI:56.8-57.8) of RSV-ALRI. Efficiency per 100,000 doses administered varied minimally across strategies. CONCLUSIONS: RSV climatic variations underscored the importance of surveillance in tailoring the timing and extent of annual campaigns. RSV seasonality informs the selection of interventions. Public health initiatives can enhance prevention for newborns by defining optimal windows for immunising at-risk-infants.
3. Adjunctive Corticosteroid Use and Clinical Outcomes in Non-HIV Pneumocystis jirovecii Pneumonia.
In 375 non-HIV PCP patients requiring oxygen, higher cumulative corticosteroid dosing over 21 days was associated with increased 90-day mortality (HR 1.01 per 100 mg prednisone-equivalent) without benefits on intubation risk or liberation from advanced respiratory support.
Impact: By modeling corticosteroid exposure as a continuous, time-varying dose, this study challenges common extrapolation from HIV-PCP and provides nuanced evidence that higher cumulative dosing may be harmful in non-HIV PCP.
Clinical Implications: Avoid escalating cumulative corticosteroid doses beyond trial-tested regimens in non-HIV PCP; prioritize antimicrobial therapy and supportive care while awaiting randomized evidence to refine steroid use.
Key Findings
- Higher cumulative corticosteroid dose over 21 days increased 90-day mortality (HR 1.01 per 100 mg prednisone-equivalent; 95% CI 1.00–1.02).
- No association between steroid exposure and risk of intubation or faster liberation from advanced respiratory support.
- 93.6% received steroids; overall 90-day mortality was 44%, with high ICU utilization (56%).
Methodological Strengths
- Marginal structural models with inverse probability weighting to address time-varying confounding
- Multicenter cohort with explicit dose–response modeling of corticosteroid exposure
Limitations
- Retrospective design with potential residual confounding and exposure misclassification
- Lack of standardized steroid protocols limits inference on optimal dosing regimens
Future Directions: Randomized trials comparing steroid dosing strategies in non-HIV PCP and mechanistic studies to identify subgroups that may benefit from adjunctive steroids.
BACKGROUND: Adjunctive corticosteroids improve outcomes in HIV-associated Pneumocystis jirovecii pneumonia (PCP), but their role in non-HIV-associated PCP is uncertain. Prior evidence largely has been limited to binary treatment groups and rarely has accounted for daily or cumulative dose effects. RESEARCH QUESTION: What is the dose-response relationship between adjunctive corticosteroids and outcomes in non-HIV immunocompromised adults with PCP requiring supplemental oxygen? METHODS: We conducted a multicenter retrospective cohort analysis of 375 non-HIV immunocompromised adults with proven or probable PCP hospitalized between 2019 and 2025. All patients were hypoxemic at treatment initiation. Corticosteroid exposure was modeled as a continuous, cumulative time-varying dose over 21 days using marginal structural models with inverse probability of treatment weighting to adjust for baseline covariates and time-varying illness severity. RESULTS: Of 375 patients, 351 patients (93.6%) received corticosteroids. The most common causes of immunosuppression were hematologic malignancy (30%), solid tumors on chemotherapy (30%), autoimmune disease (17%), and solid organ transplantation (14%); 56% of patients required ICU admission and 44% of patients died within 90 days. Greater cumulative steroid dose was associated with increased risk of 90-day mortality (weighted hazard ratio [HR], 1.01 per 100 mg prednisone-equivalent; 95% CI, 1.00-1.02; P = .006). Steroid exposure was not associated with risk of intubation (HR, 0.99; 95% CI, 0.97-1.02) or faster liberation from advanced respiratory support (HR, 1.00; 95% CI, 0.98-1.02). INTERPRETATION: In patients with non-HIV PCP with hypoxemia, higher cumulative corticosteroid exposure was not associated with improved respiratory outcomes and was linked to increased mortality. Use of doses exceeding trial-tested regimens should be approached with caution.